1. Field of the Invention
The present invention relates generally to compositions and methods useful to treat autoimmune diseases. More specifically, the invention relates to compositions of reduced isoalpha acids, minerals and vitamins.
2. Description of the Related Art
Autoimmune diseases and disorders occur when the body's own protective immune system becomes self destructive. The targets of autoimmune interaction can range anywhere from the cellular level (e.g., myelin basic protein in multiple sclerosis, or the thyrotropin receptor in Graves' disease) to organ specific effects in rheumatoid arthritis or Crohn's disease to system wide effects as seen in systemic lupus erythematosus. Some of the events that have been postulated in the causation of autoimmune diseases have included cytokine over expression, for example TNF-α, IL-2, or IL-2 receptor in inflammatory bowel disease, or under expression (IL-10 under expression in Type 1 diabetes), to defects in allele expression (HLA Class I B27 in ankylosing spondylitis), to altered expression of apoptosis proteins (under expression of Fas in autoimmune lymphoproliferative syndrome type 1 (ALPS 1). See Harrison's Principles of Internal Medicine, 16th ed., McGraw-Hill, New York, 2005; Chapter 295 for additional information on autoimmune diseases.
Inflammation, while not causative of many autoimmune diseases, none the less is a symptom often associated with autoimmune diseases and disorders, such as, for example, rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, or ulcerative colitis. As such, anti-inflammatory agents are often incorporated into many autoimmune treatment modalities as a means of palliative relief.
Compounds that inhibit the production of prostaglandin (PG)s have become important drugs in the control of pain and inflammation. Collectively these agents are known as non-steroidal anti-inflammatory drugs (NSAIDs) with their main indications being osteoarthritis and rheumatoid arthritis. Arachidonic acid serves as the primary substrate for the biosynthesis of all PGs. PGs are ubiquitous hormones that function as both paracrine and autocrine mediators to affect a myriad of physiological changes in the immediate cellular environment. The varied physiological effects of PGs include inflammatory reactions such as in rheumatoid arthritis and osteoarthritis, blood pressure control, platelet aggregation, induction of labor and aggravation of pain and fever.
In addition to prostaglandins, recent research has shown that trace metal levels of zinc and selenium may have a possible role in the etiology and pathogenesis of osteoarthritis and rheumatoid arthritis. Plasma and synovial fluid Se concentration were found to be significantly lower (p<0.05, and p<0.05, respectively), whereas Cu concentrations were significantly higher in patients with rheumatoid arthritis than those of healthy subjects. The investigators additionally identified a significantly positive correlation between synovial fluid Se—Cu values and Zn—Fe values in patients with rheumatoid arthritis (see Yazar, M., et al., Biol. Trace Elem Res 106(2): 123-132, 2005; McConnell, K. P., et al., J. Nutr. 105(8): 1026-1031, 1975). This suggests that trace metal supplementation may be advantageous in ameliorating some of the symptoms associated with rheumatoid arthritis by bringing those trace element levels to a more normal level.
Further, it has long been known that the macrophage is a potent mediator of immune reactions and that rheumatoid arthritis is characterized by a migration of activated phagocytes (and other immunoreactive cells) into synovial and periarticular tissue. The activated phagocytes, upon reaching the synovia release numerous mediating substances that appear to both exacerbate and perpetuate the rheumatoid condition. Pharmacological doses of zinc may immobilize macrophages, thereby preventing or limiting their access to the synovial site and providing a potential means to reduce joint specific inflammation in rheumatoid arthritis. See, for example, Aaseth, J., et al., Analyst 123(1): 3-6, 1998). Additionally, macrophage immobilization may play a role in reducing macrophage interaction and activation, thereby reducing possible participation in, or augmentation of, the autoimmune response.
Therefore, it would be useful to identify compositions and methods that would modulate prostaglandin levels and or regulate macrophage activity, thereby modulating the inflammatory response associated with many autoimmune diseases. Such modulation and use may require continual use for chronic conditions or intermittent use as needed. Additionally, supplementation with select trace metals may also serve a means towards restoring a more normal immune function, thereby offering an additional avenue for intervention in autoimmune diseases. The instant invention describes compounds, compositions and methods to treat inflammation and autoimmune diseases related symptoms with a concomitant increase in the quality of life.